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Evaluation of Forkhead BOX M1 (FOXM1) gene expression in colorectal cancer

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Abstract

Forkhead Box M1 (FOXM1)—a key cell cycle regulator is a member of the Forkhead transcription factor family. It plays a key role in embryogenesis and cell proliferation and has been strongly linked to various solid tumors. We sought to understand the regulation of FOXM1 in colorectal cancer (CRC), as well as if and to what extent other clinicopathological characteristics are associated with FOXM1. The investigation comprised 98 CRC samples and normal tissues (controls). All colon cancer patients had a colonoscopy and targeted biopsy. All rectal cancer patients had a CT and MRI. Real-time PCR, Immunohistochemistry, and Western blotting were used to evaluate FOXM1 expression, and the findings were analyzed using SPSS (v.26). FOXM1 mRNA and protein expression were substantially upregulated in tumor tissues, with the majority of these proteins localized in nucleo-cytoplasm. Elevated protein levels of FOXM1 were strongly correlated with lower education level, larger tumor size, lymph node status, lymphovascular invasion (LVI), perineural invasion (PNI), lymph node metastasis (LNM), tumor invasion depth (subserosal and serosal invasion), late stage (III and IV), localization (nucleo-cytoplasmic), intensity (strong) and recurrence. Based on survival analysis, FOXM1 overexpression and nucleo-cytoplasmic localization were associated with shorter disease-free survival while stage and PNI were linked to poorer overall and disease-free survival. According to the results of the Cox regression analysis, stage and PNI were significant predictors of prognosis in CRC patients. FOXM1 expression was elevated in CRC and was linked to reduced disease-free survival. These findings support prior reports and hence FOXM1 can be an important prognostic marker for CRC and a promising therapeutic target. Additionally, we found a link between poor disease-free survival and FOXM1's nucleo-cytoplasmic localization. However, since the sample size of this study was small, further research is needed to validate our findings.

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Acknowledgements

The authors would like to thank patients who agreed to take part in this study. The authors would also like to thank the technical personnel of the Department of General Surgery and Pathology for their assistance in obtaining tissue samples and tissue blocks. The authors are thankful to Dr. Syed besina and Dr. Ishrat Younas Khan for providing support for IHC experimental and evaluation analysis

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  1. Ishrat Parveiz and Gulzar A. Bhat contributed equally as 2nd author.

Authors and Affiliations

  1. Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, 190011, India

    Tahseen Bilal Rather, Ishrat Parveiz, Gulzar A. Bhat, Gowhar Rashid & Syed Mudassar

  2. Department of Medical Lab Technology, Amity Medical School, Amity university, Haryana, India

    Gowhar Rashid

  3. Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, 190011, India

    Rauf A. Wani

  4. Department of Pathology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, 190011, India

    Ishrat Younas Khan

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Contributions

TBR wrote the manuscript and did the experimental work. IP and GAB revised the manuscript and assisted in data analysis. GR helped with data collection. RAW provided access to tissue samples. IYK helped in pathological data interpretation. SM drafted the overall design of this study and provided experimental support.

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Correspondence to Syed Mudassar.

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The original online version of this article was revised: Modifications have been made in tables 3, 4, 5 and 7 and in the text. Full information regarding the corrections made can be found in the erratum for this article.

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Rather, T.B., Parveiz, I., Bhat, G.A. et al. Evaluation of Forkhead BOX M1 (FOXM1) gene expression in colorectal cancer. Clin Exp Med 23, 2385–2405 (2023). https://doi.org/10.1007/s10238-022-00929-7

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